Pretrichodermamide C and N-methylpretrichodermamide B, two new cytotoxic epidithiodiketopiperazines from hyper saline lake derived Penicillium sp.

Orfali, Raha; Aly, Amal H.; Ebrahim, Weaam; Abdel‐Aziz, Mohamed S.; Müller, Werner; Lin, Wenhan; Proksch, Peter

doi:10.1016/j.phytol.2014.12.010

Cited by 40 publications

(42 citation statements)

References 29 publications

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“…23, 24 One of these compounds, N-methylpretrichodermamide B ( 19 ), was found to be cytotoxic in highly drug-resistant prostate cancer cell lines (IC 50 = 0.51-5.11 μM) 23 as well as in a murine lymphoma cell line (IC 50 = 2 μM), 24 while only cytotoxic to nonmalignant murine cells at much higher concentrations. 23 Interestingly, the cytotoxic pretrichodermamide 19 contains a chloride moiety at carbon 5, while the noncytotoxic compounds 20 - 23 lack this feature.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity and Mechanism of Action of the Marine-Derived Fungal Metabolite Trichodermamide B and Synthetic Analogues

et al. 2017

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The trichodermamides are modified dipeptides isolated from a wide variety of fungi, including Trichoderma virens. Previous studies reported that trichodermamide B (2) initiated cytotoxicity in HCT-116 colorectal cancer cells, while trichodermamide A (1) was devoid of activity. We recently developed an efficient total synthesis for the trichodermamides A–C (1–3). Multiple intermediates and analogues were produced, and they were evaluated for biological effects to identify additional structure activity relationships and the possibility that a simplified analogue would retain the biological effects of 2. The antiproliferative effects of 18 compounds were evaluated and the results show that 2 and four other compounds are active in HeLa cells, with IC50 values in the range of 1.4–21 μM. Mechanism of action studies of 2 and the other active analogues revealed different spectra of activity. At the IC85 concentration, 2 caused S-phase accumulation and cell death in HeLa cells, suggesting response to DNA double strand breaks. The analogues did not cause S-phase accumulation or induction of DNA damage repair pathways, consistent with an alternate mode of action. The mechanistic differences are hypothesized to be due to the chlorohydrin moiety in 2 which is lacking in the analogues, which could form a DNA-reactive epoxide.

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Section: Resultsmentioning

confidence: 99%

Cytotoxicity and Mechanism of Action of the Marine-Derived Fungal Metabolite Trichodermamide B and Synthetic Analogues

et al. 2017

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“…The identification was performed according to a molecular biological protocol by DNA amplification and sequencing of the ITS region (GenBank accession no. KP013122) as described previously (Orfali et al, 2015;Kjer et al, 2010). The fungal strain was cultivated on solid rice medium, which was prepared by autoclaving 100 g of rice and 100 mL of 3.5% sea salt in water in a 1 L Erlenmeyer flask.…”

Section: Fungal Materialsmentioning

confidence: 99%

“…As negative controls, media with 0.1% EGMME-DMSO was included in the experiments. The cytotoxic depsipeptide kahalalide F, which was isolated from Elysia grandifolia, was used as a positive control (Orfali et al, 2015;Ashour et al, 2006).…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

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Isochroman and isocoumarin derivatives from hypersaline lake sediment-derived fungus Penicillium sp.

Orfali

Aly

Ebrahim

et al. 2015

Phytochemistry Letters

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“…, N -methylpretrichodermamide B ( 6 ) and pretrichodermamide C ( 7 ) from Penicillium sp. , 7 gliovirin ( 8 ) from Trichoderma virens , 8 and FA-2097 ( N -methylgliovirin, 9 ) from Eupenicillium abidjanum . 9 In addition, the structurally related aspergillazines BE ( 10–13 ) from A. unilateralis are presumed to arise from the reductive N–O bond cleavage of aspergillazine A (for B and C) and trichodermamide A (for D and E).…”

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confidence: 99%

Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core

Mfuh

Stephens

et al. 2015

J. Am. Chem. Soc.

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We report herein a facile and efficient method of the construction of the cis-1,2-oxazadecaline system, distinctive of (pre)trichodermamides, aspergillazine A, gliovirin and FA-2097. The formation of the 1,2-oxazadecaline core was accomplished by a 1,2-addition of an αC-lithiated O-silyl ethyl pyruvate oxime to benzoquinone, that is followed by an oxa-Michael ring-closure. The method was successfully applied to the concise total synthesis of trichodermamide A (in gram quantities), trichodermamide B, as well as the first synthesis of trichodermamide C.

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Pretrichodermamide C and N-methylpretrichodermamide B, two new cytotoxic epidithiodiketopiperazines from hyper saline lake derived Penicillium sp.

Cited by 40 publications

References 29 publications

Cytotoxicity and Mechanism of Action of the Marine-Derived Fungal Metabolite Trichodermamide B and Synthetic Analogues

Cytotoxicity and Mechanism of Action of the Marine-Derived Fungal Metabolite Trichodermamide B and Synthetic Analogues

Isochroman and isocoumarin derivatives from hypersaline lake sediment-derived fungus Penicillium sp.

Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core

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